Preparation of 2-mercapto thiazoles



Patented July 15, 1952 PREPARATION or z-mnncar'ro THIA James T. Gregory, Akron,

B. F. Goodrich Company, New York, N.

zoLEs Ohio, assignor to The Y., a

corporation of New York No Drawing. Application October 18, 1951, Serial N0. 251,997

-This invention relates to a novel reaction of alpha-thiocyano carbonyl compounds and more specifically pertains to the reaction of alpha-thiccyano carbonyl compounds with thiourea whereby -a;2-mercapto thiazole is formed.

I have discovered that an alpha-thiocyano carbonyl compound; that is, an aldehyde or ketone having athiocyano group attached to the carbon which is immediately adjacent to the carbonyl carbon of the aldehyde or ketone, will react with thiourea in the presence of an aqueous medium acidified with mineral acid to produce a 2-mercapto thiazole with the formation of cyanamide and splitting out of water. This reaction is believed to take place as follows:

R1-,C=O

wherein R1 and R2 comprise the non-reactive residue of the thiocyano carbonyl. Generally R1 and R2 are hydrogen or hydrocarbon radicals containing from 1 to carbon atoms.

.It is believed that the thiocyano carbonyl re,- acts with the thiourea first splitting out water to close the thiazole ring to form a non isolatable intermediate having the probable structure Then on heating during the reaction, cyanamide splits ofi and the mercapto group is formed. The

cyanamide can be recovered, with H28 in the presence of ammonia to prepare more thiourea.

This novel reaction provides a new method for preparing 2-mercaptothiazoles. It is a particular- 1y useful process and has many advantages over the prior art-methods for preparing Z-mercaptothiazoles. The methods for the preparation of 2- mercaptothiazoles which .the* prior art discloses and which have been employed in industrial preparations of 2-mercaptothiazoles involve the use of and may be reacted 3 Claims. (Q1: 260-.-r3.02)

chlorinated reactants, especially alpha-chloro ketones. These 'chlor'o ke'tones'are, in general, lachr rymators and cause no little discomfort when,

through leaks in the processing equipment, they escape to the atmosphere in which the chemical operators work. Also thesechloroketones attack' many of the materialsemployed in making gas kets, and, therefore, not only require the use of special gasket materials but also enhance the opportunities for'leaks. 1 In addition the chloro ketbneswhen by chance come into contact with skin, cause burning which results in painful slowhealing blistering of the skin. The alpha-thiccyano carbonyl compounds employed as reactants the process of this invention do not possess any of these undesirable properties.

Furthermore the chloroketones employed in the methods of the prior art require the use of elemental chlorine in their preparation. In times of national emergency and in periods ofexpam sion of the chemical industry, the supply of elemental chlorine does not meet the demand Itbecomes, therefore, essential that theavailable supply of chlorine be employed wherethere is no substitute for this versatile-element. The'2- mercaptothiazolesarewidely used in large quantities as accelerators for, the vulcanization-of natural and crude rubber compositions. Hence the discovery-oi; a' nonechlorinated reactant which can beemployed'in the preparation of" these important thiazolederivatives aids the chemical industry in releasing ichlorine' for. the

preparation of other essential. products while still providing an ample supply of accelerator for the rubber industry. n

In the process of this invention there-can b employed any alphathiocyano "carbonyl compound. Such acompound,'will of course, con

tain the structure 1 vO SON it will contain, in addition to the carbonyl ox gen atom and the nitrogen and'sulfur atoms of the Alpha-isopropyl-alpha-thiocyano-acetaldehyde,

' 3-thi6cyano-butanone-2:

-p-tolyl-..3-thiocyano-pentanone-2; I, 3-thiocyano-lpentenone=2;

V thiocyano group only carbon and hydrogen atoms as when it possesses the structure wherein R1 and R2 are hydrogen or hydrocarbon groups; however, R1 and R2 may also be radicals containing elements other than carbon and hydrogen present in non-reactive structure, as, for example,'oxygen in ether linkages',sulfur in thioether' linkages, nitrogen and oxygen in nitro groups, etc. All such alphathiocyano aldehydes and ketones are known types of compounds and can be readilyprepared by the reaction of thiocyanogen with an aldehyde or ketone as follows: 1 p- As examples of alpha-thiocyano carbonyl compounds which are suitable reactants for the process of this-invention, there maybe ,mentioned such alpha-thiocyano-aldehydes as:

and such alpha-thiocyano ketones as for exam yano propanoneq;

3-thiocyano-pentanone-2 V 3-thiocyanoehexanone-2;

BethiQcyanQ-heptanone-Z;' 3- phenyl-3 -thiocyanopropa,none-2;

. 3-oyclohex-yl-3-thiocyanopropanone2 4-phenyl 3fthiocyano butanoned 5-phenyl-3-thiocyano-pentanone-2;

fi-phenyl-3-"thiocyano-hexanone-2;'- 3-jnaphthyl-3 thiocyaho-propanone-z;

2-tliiocyano-pentanon'e-3; 2-thiocyano-hexan'one-3; 1thiocyan0-Ihexanone-2;. I Alpha-thiocyano propionophenone,

' 1-pheny1- 3-thiocyano.-butanone-2;

1 -phenyl-4-lthiocyano -pentanone-3 Alpha-thiocyano propiononaphthone; 4-thiocyano-hexanone-3; l s-thiocyano-heptanone-l; 2-thiocyano-octanone-3 Alpha-thiocyano-pentanophenone; 1-phenyl-3-thiocyanoepentanone-2; 1-phenyl-4-thiocyano-hexanone-3; Alpha-thiocyano-pentanonaphthone; 5-thiocyano-1heptenone-4;; l-cyclohexyl-l-thiocyan0-propanone; 1-cyclohexyl-2-thiocyano-propanone; I 1-cyclohexyl-2ethiocyano butanone; 1-methoxy-3-thiocyanobutanone-2;

1 (methyl-thio) -3 -thiocyanobutanone-2; 2 thiocyano-l-isopropoxy-butanone-3; 2-thiocyano-1- (isopropyl-thio) -butanone-3; 2-thiocyano-1 -ethoxy-butanone-3 Z-thiocyano-l- (ethyl-thio) -butanone-3; 2-thiocyano-1 -o-nitrophenyl-butanone-3 2-thiocyano-1,S-di-phenyl-6-nitrohexanone-3; 3-thiocyano-1-butoxy-2-methylhexanone-4; 4-thiocyano-1 -ethoxye5-methylhexanone-3 2-thiocyano-cyclopentanone; 2-thiocyano-cyclo-hexanone;

' 2,5-di.(thiocyano)-1,4-cyclohexanedione;

2,3-di(thiocyano) -1,4-cycloliexanedione; 1 2,3di(thiocyano)-1,4-pentanedione; 2,5-di (thiocyano) -1,6-decanedione and 2- alpha-thiocyanoacetonyl) -cyclohexanone.

Although any alpha-thiocyano carbonyl compound containing the structure hereinbefore set forth can be employed as a reactant according to the process of this invention, the alpha-thiocyano I :ketones, where R1, in the general formula hereinbefore appearing, is a hydrocarbon group are the proportions of at least one mole and pref erably two or more molesof thieurea 'pe'rrm'ole of the thiocyano carbonyl. Awat er-miscible sol-" vent which facilitates solution of thiourea can also be added if desired. This mixture is stirred for a substantial time interval. It is preferred to carry out the reaction at the reflux temperature I of the reaction mixture. The 2-mercaptothiazole the chemical reaction preferred as reactants because at present they are more readily available.

Any of the mineral acids such as hydrochloric, sulfuric, phosphoric, and other mineral aicids can be employed in the process of this invention, but

hydrochloric acid is the preferred mineral acid for this process. The quantity of acid to be em -ployed in the process of this invention can be" per mole of thioureal varied from about one mole to two or more moles A more 'detailedi'description of the process of? this invention is as follows} To an aqueous solu--. tion containing the mineral acid there is added" a thiocyano carbonyl compound and thioureain and heated to a temperature of from 50 to C.

is formed during the reaction as a crystalline precipitate which is easily recovered from the aqueous reaction medium.

illustrate the process of this invention.

The following specific example will further.

. EXAMPLE There was charged. to areactor containing 40 parts byweight of ethanol a'nd2'76 of a dilute aqueous solution containinglfl parts by, weight of HCl; 12.9 parts by'weight'of. 3'-'thio'-' cyanobutanoneZ and 15.2,parts by...v weight of thiourea. The resulting mixture was stirred and heated to reflux temperature (86 C.) for ten hours. During reflux a crystalline precipitate formed which was recovered by filtration. This product had a melting point of 158 to 162 zC; Afte'r'two recrystallizations from an 8 to l mixture of'water'and ethanol the" purified product was a light'yellow crystalline solid melting at. 16l'.5'to 164.5" C. Ultra violet absorption spectrum'of this productwas identical with that of Z-mercapto- 4,5-dimethylthiazole. Therefore the product of methylthiazole.

The following examples" in tabular? form' are I presented .to illustrate the variety of 2-mercapto- .thiazoles which can be prepared according to the process of this invention parts by Weight was 7 Z-mercapto-h-di- I 2,603,648 5 6 Products of reaction of thiourea with an alphathiocyano carbonyl compound g g Thiocyano Carbonyl 7 Product l-thiocyanobutanone-2 2-mercapto-4-ethylthiazole. Thiocyano acetaldehyde 2-mercaptothiazole. Alpha-thiocyanopropiona1dehyde 2-mercapto-5-methylthiazole.

2-isopropyl-2-tl1iocyano aceta1dehyde 2-mercapto-5-isopropylthiazole. I 2-phenyl-2-thiocyano acetaldehyde... 2-mercapto-5-phenylthiazole.

Z-mercapto-5-propyl-4'methy1-thiazo1e. Z-mercapto-5-benzyli-methyl-thiazole.

3-thiocyano hexanone-2 .+phenyl-3-thiocyano-butanone-2 2-thiocyano-heptanone-3 Z-mercapto-4-methyl-5-n-butylthiazole. 0 2-mercapto4 methyl-fi-phenylthiazole. Ot'J-oH-o H:

.SCN

Alpha-thiooyano propiono-phenone 2-mercapto-4-phenethyl-5-ethyl-thiazole. 2-mereapto-4 allyl-5-ethyl-thiazole. 2-m ercapto-4-methyl-5-a1ly1-thiazo1e.

l-pheny1-4-thiocyano hexanone-3.

5-thiooyano-l-heptenone-4 3-thiocyano-4-hexenone-2 Any of the other thiocyano carbonyl compounds 2. The method which comprises reacting thio! the class hereinbefore defined can be employed so ourea with an alphathiocyano carbonyl comas a reactant in place of those employed in the pound having the structure above examples to produce corresponding 2-mercaptothiazoles.

Although I have illustrated my invention with R1 O CH"R' the preparation of certain specific 2-mercapto- 35 mm thia'zolesr employing Special tmocyano carbonylsr wherein R1 and. R2 are members selected from I do not thereby desire intend to limit the class consisting of hydrogen and hydrocarbon self solely thereto, for as hitherto stated reactants groups containing from 1 to 10 carbon atoms, in which are the 011911119911 equlvalents of 1111056 40 the presence of a dilute aqueous solution of HCl p d may be substltuted r the speclfic reac and at reflux temperature, thereby to form a 2- tants used i the e p s and pl'facise P mercaptothiazole and recovering said thiazole. portions of the reactants can be varied, 1f des 3. The method which comprises reacting at rewithout dep r qm the Spirit and s p 0f the flux temperature 3-thiooyanobutanone-2 with invention as defi ed 1n the pp clalmsthiourea in the presence of a diluteaqueous solu- I claim: tion of HCl thereby to form 2-mercapto-4,5-di- 1. The method w h P reactmg an methylthiazole, and recovering said thiazole. alpha-thiocyano carbonyl with thiourea in the JAMES Y,

presence of a dilute aqueous solution of a minc al acid thereby to fo m a .-m r p h re ee g No references cited. 

1. THE METHOD WHICH COMPRISES REACTING AN ALPHA-THIOCYANO CARBONYL WITH THIOUREA IN THE PRESENCE OF A DILUTE AQUEOUS SOLUTION OF AN MINERAL ACID THEREBY TO FORM A 2-MERCAPTOTHIAZOLE. 